Partial aortic occlusion devices and methods for cerebral perfusion augmentation

ABSTRACT

Methods are provided for partial aortic obstruction for cerebral perfusion augmentation in patients suffering from global or focal cerebral ischemia. Alternatively, the methods can be used to partially obstruct aortic blood flow to condition the spinal cord to secrete neuroprotective agents prior to abdominal aortic aneurysm repair. Partial obstruction of a vessel can be accomplished by a device comprising an elongate catheter and a distally mounted expandable member. The expandable member may comprise one or two balloons. Other medical devices, such as an angioplasty, stent, or atherectomy catheter, can be inserted distal the expandable member to provide therapeutic intervention.

This is a continuation of U.S. application Ser. No. 11/042,639, filedJan. 24, 2005 now U.S. Pat. No. 7,867,195, which is a continuation ofU.S. application Ser. No. 10/052,688, filed Jan. 18, 2002 now abandoned,which is a continuation of U.S. application Ser. No. 09/841,929, filedApr. 24, 2001, now U.S. Pat. No. 6,743,196, all of which areincorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates generally to medical devices. Moreparticularly, the invention relates to methods and devices foraugmenting blood flow to a patient's vasculature. More particularly, theinvention relates to apparatus and methods which provide partialobstruction (“coarctation”) to aortic blood flow to augment cerebralperfusion in patients with global or focal ischemia. The devices andmethods also provide mechanisms for continuous constriction and variableblood flow through the aorta.

BACKGROUND OF THE INVENTION

Patients experiencing cerebral ischemia often suffer from disabilitiesranging from transient neurological deficit to irreversible damage(stroke) or death. Cerebral ischemia, i.e., reduction or cessation ofblood flow to the central nervous system, can be characterized as eitherglobal or focal. Global cerebral ischemia refers to reduction of bloodflow within the cerebral vasculature resulting from systemic circulatoryfailure caused by, e.g., shock, cardiac failure, or cardiac arrest.Shock is the state in which failure of the circulatory system tomaintain adequate cellular perfusion results in reduction of oxygen andnutrients to tissues. Within minutes of circulatory failure, tissuesbecome ischemic, particularly in the heart and brain.

The two common forms of shock are cardiogenic shock, which results fromsevere depression of cardiac performance, and hemorrhagic shock, whichresults from trauma. The most frequent cause of cardiogenic shock ismyocardial infarction with loss of substantial muscle mass. Pump failurecan also result from acute myocarditis or from depression of myocardialcontractility following cardiac arrest or prolonged cardiopulmonarybypass. Mechanical abnormalities, such as severe valvular stenosis,massive aortic or mitral regurgitation, acutely acquired ventricularseptal defects, can also cause cardiogenic shock by reducing cardiacoutput. Additional causes of cardiogenic shock include cardiacarrhythmia, such as ventricular fibrillation. Hemorrhagic shock istypically the result of penetrating injuries caused by, for example,traffic accidents and gunshot wounds. In this case, cardiac function isunimpaired and the cause of shock is blood loss.

Treatment of global cerebral ischemia involves treating the source ofthe systemic circulatory failure and ensuring adequate perfusion to thecentral nervous system. For example, treatment of cardiogenic shock dueto prolonged cardiopulmonary bypass consists of cardiovascular supportwith the combination of inotropic agents such as dopamine, dobutamine,and intra-aortic balloon counterpulsation. Treatment of hemorrhagicshock consists of volume replacement and hemostasis. When these measuresfail, supracoeceliac aortic clamping is used. Vasoconstrictors, such asnorepinephrine, are also administered systemically to maintain systolicblood pressure (ideally above 80 mmHg). Unfortunately, these agentsproduce a pressure at the expense of flow, particularly blood flow tosmall vessels such as the renal arteries. The use of thevasoconstrictors is, therefore, associated with significant sideeffects, such as acute renal failure, congestive heart failure, andcardiac arrhythmias.

Focal cerebral ischemia refers to cessation or reduction of blood flowwithin the cerebral vasculature resulting from a partial or completeocclusion in the intracranial or extracranial cerebral arteries. Suchocclusion typically results in stroke, a syndrome characterized by theacute onset of a neurological deficit that persists for at least 24hours, reflecting focal involvement of the central nervous system and isthe result of a disturbance of the cerebral circulation. Other causes offocal cerebral ischemia include vasospasm due to subarachnoid hemorrhageor iatrogenic intervention.

Traditionally, emergent management of acute ischemic stroke consists ofmainly general supportive care, e.g. hydration, monitoring neurologicalstatus, blood pressure control, and/or anti-platelet or anti-coagulationtherapy. Heparin has been administered to stroke patients with limitedand inconsistent effectiveness. In some circumstances, the ischemiaresolves itself over a period of time due to the fact that some thrombiget absorbed into the circulation, or fragment and travel distally overa period of a few days. In June 1996, the Food and Drug Administrationapproved the use of tissue plasminogen activator (t-PA) or Activase®,for treating acute stroke. However, treatment with systemic t-PA isassociated with increased risk of intracerebral hemorrhage and otherhemorrhagic complications. Vasospasm may be partially responsive tovasodilating agents. The newly developing field of neurovascularsurgery, which involves placing minimally invasive devices within thecarotid arteries to physically remove the offending lesion may provide atherapeutic option for these patients in the future, although this kindof manipulation may lead to vasospasm itself. Iatrogenic vasospasm andvasospasm caused by subarachnoid hemorrhage may respond to treatmentwith aortic constriction.

In both global and focal ischemia, patients develop neurologic deficitsdue to the reduction in cerebral blood flow. One treatment may includethe use of devices to increase blood flow to the cerebral vasculature asthe sole therapy. Alternatively, treatments include measures to increaseblood flow to the cerebral vasculature to maintain viability of neuraltissue, thereby increasing the length of time available for any adjunctinterventional treatment and minimizing neurologic deficit while waitingfor resolution of the ischemia. Augmenting blood flow to the cerebralvasculature is not only useful in treating occlusive or vasospasticcerebral ischemia, but may also be useful during interventionalprocedures, such as carotid angioplasty, stenting or endarterectomy,which might otherwise result in focal cerebral ischemia, and alsocardiac procedures which may result in cerebral ischemia, such ascardiac catheterization, electrophysiologic studies, and angioplasty.

New devices and methods are thus needed for augmentation of cerebralblood flow in treating patients with either global or focal ischemiacaused by reduced perfusion, thereby minimizing neurologic deficits.

SUMMARY OF THE INVENTION

In one embodiment, the invention provides vascular obstruction,occlusion, and/or constriction devices and methods for augmenting bloodflow to a patient's cerebral vasculature, including the carotid andvertebral arteries. The terms obstruction, occlusion, and constrictionare used interchangeably herein to refer to partial or complete blockageof a vessel, and to any of the devices that provide such blockage. Thedevices comprise an obstructing, occluding, or constricting mechanismdistally mounted on a catheter for delivery to a vessel, such as theaorta. The obstructer, occluder, and/or constrictor is collapsed tofacilitate insertion into and removal from the vessel, and expandedduring use to at least partially obstruct blood flow.

In one embodiment, the devices comprise an elongate catheter having aproximal and a distal region. The catheter may also have a lumenextending between the proximal and distal regions. An expandable device,e.g., a balloon in certain cases, is carried at the distal region of thecatheter. The catheter in certain embodiments may include a secondexpandable device carried at the distal region of the catheter, proximalthe first expandable device. In certain embodiments, the catheter willalso include blood pressure measuring capabilities distal and/orproximal the first and/or second (when present) expandable devices.

In use, the catheter having one expandable device is located in thedescending aorta so that the expandable device is suprarenal orinfrarenal. The expandable device is then expanded to partially orcompletely obstruct the descending aorta. Cerebral blood flow andcerebral blood pressure rises and is maintained at an increased level asdesired. Cephalad blood pressure and/or cerebral blood flow may bemonitored, and the expandable device adjusted as needed. Therapeuticinstruments may be deployed through the lumen (when present) of thecatheter to perform procedures cephalad.

In another embodiment, the constrictor, when expanded, has a maximumperiphery that conforms to the inner wall of the vessel, therebyproviding a sealed contact between it and the vessel wall. Theconstrictor typically has a blood conduit allowing blood flow from alocation upstream to a location downstream. The devices further includea variable flow mechanism in operative association with the bloodconduit, thereby allowing blood flow through the conduit to be adjustedand controlled. The devices can optionally include a manometer and/orpressure limiter to provide feedback to the variable flow mechanism forprecise control of the upstream and downstream blood pressure.

In certain embodiments, the constrictor includes a second lumen forpassage of other medical devices. Devices, such as an infusion,atherectomy, angioplasty, hypothermia catheters or devices (selectivecerebral hypothermia with or without systemic hypothermia, and typicallyhypothermia will be combined with measures to increase perfusion toovercome the decreased cerebral blood flow caused by the hypothermia,such that hypothermia and coarctation are complimentary), orelectrophysiologic study (EPS) catheter, can be introduced through theconstrictor to insert in the vessel to provide therapeutic interventionsat any site rostrally. Where cerebral cooling is desired in combinationwith coarctation, a cooling wire can be introduced through theconstrictor to insert into a desired vessel. Alternatively, coolingcatheter devices can be inserted through the constrictor to infuse coolblood selectively into one side of the brain. Devices and methodsdescribed in U.S. application Ser. Nos. 09/792,732, filed Feb. 23, 2001;09/792,600, filed Feb. 23, 2001; 09/483,370, filed Jan. 14, 2000;09/256,965, filed. Feb. 24, 1999, now abandoned; 60/076,222, filed Feb.25, 1998, now abandoned; 60/096,218, filed Aug. 12, 1998, now abandoned;and U.S. Pat. Nos. 6,161,547, 6,165,199, and 6,146,370, all incorporatedherein by reference in their entirety, can be used for cooling or otherprocedures.

In another embodiment, the expandable constrictor comprises an outerconical shell and an inner conical shell. Each shell has an apex and anopen base to receive blood flow. One or a plurality of ports traversesthe walls of the two conical shells. Blood flows through the open baseand through the ports. The inner shell can be rotated relative to theouter shell so that the ports align or misalign with the ports in theouter shell to allow variable blood flow past the occluder, therebyproviding adjustable and controlled flow. The inner shell is rotated bya rotating mechanism, e.g., a torque cable disposed within the elongatetube and coupled to the inner shell. The constrictor can be expanded by,e.g., a resilient pre-shaped ring, graduated rings, or a beveled lipformed at the base of the shell, and collapsed by, e.g., pull wiresdistally affixed to the occluder or a guide sheath.

In another embodiment, the outer conical shell includes a plurality ofresilient flaps, which are pivotally affixed to the base or the apex andcan be displaced to variably control blood flow through the conduit. Theflaps can be displaced by a plurality of pull wires affixed to theflaps.

In still another embodiment, the constrictor comprises a firstcylindrical balloon mounted to a distal end of the catheter, and asecond toroidal balloon disposed about the cylindrical balloon. Thechamber of the first balloon communicates with an inflation lumen. Bloodflow occurs through the cylindrical balloon and through the center ofthe toroidal balloon. The toroidal balloon is expanded by inflationthrough a second and independent inflation lumen to reduce blood flowthrough the cylindrical balloon. In this manner, the first balloonprovides an inflatable sleeve and the second toroidal balloon providesvariable control of blood flow through the sleeve. Other embodimentsinclude an expandable sleeve (not a balloon) surrounded by a toroidalballoon, or a spring mechanism, for adjustably constricting the flow ofblood through the cylindrical sleeve.

In use, the obstruction/occlusion/constriction devices described aboveare inserted into the descending aorta through an incision on aperipheral artery, such as the femoral, subclavian, axillary or radialartery, in a patient suffering from global or focal cerebral ischemia,typically stroke, shock or vasospasm, or during cardiac surgery(including any operation on the heart, with or without CPB), or duringaortic surgery (during circulatory arrest, as for aortic arch surgery,repair of an abdominal aortic aneurysm, or thoracic aneurysm repair, toreduce perfusion and the amount of blood loss in the operating field).The devices can be introduced over a guide wire.

With assistance of transesophageal echocardiography (TEE), transthoracicechocardiography (TTE), intravascular ultrasound (IVUS), aortic archcutaneous ultrasound, or angiogram, the constrictor is positioneddownstream from the takeoff of the brachiocephalic artery and upstreamfrom the renal arteries. When the constrictor is inserted in itspreferred position, i.e., below the renal arteries, no visualization isnecessary with any imaging equipment. The constrictor is expanded to atleast partially obstruct blood flow in the aorta and maintained duringsystole, during diastole, or during systole and diastole. Theconstrictor preferably achieves continuous apposition to the wall of thevessel, resulting in reduced embolization. The pressure limiter,connected to the rotary unit and the pressure monitor, prevents theupstream and downstream blood pressure from exceeding, respectively, aset maximum and minimum pressure differential.

Flow rates can be varied within one cardiac cycle (e.g., 80% duringsystole, 20% during diastole, or 70% during systole, 30% duringdiastole), and every few cycles or seconds (e.g., 80% for 6 cycles, 20%for 2 cycles, or 70% for 5 cycles, 10% for 1 cycle). In certain cases itmay be preferred to cycle between lesser and greater occlusion so thatthe brain does not autoregulate. This ensures constant and continuedincreased cerebral perfusion. In this manner, blood in the descendingaorta is diverted to the cerebral vasculature, thereby increasingcerebral perfusion and minimizing neurological deficits. By selectivelyincreasing cerebral blood flow, the use of systemically administeredvasoconstrictors or inotropic agents to treat shock may be reduced oreliminated.

In another method, in patients anticipating a major cardiothoracicsurgery, such as abdominal aortic aneurysm repair, the device isintroduced and deployed approximately 24 hours prior to surgery, therebyinducing mild artificial spinal ischemia. This induces endogenousneuroprotective agents to be released by the spinal cord and/or brain inresponse to the ischemia, thereby protecting the tissue from ischemicinsult of surgery. This technique is known as “conditioning.” Thedevices are inserted into the descending aorta. To induce spinalischemia, the constrictor is positioned downstream from the takeoff ofthe brachiocephalic artery and upstream from the renal artery andexpanded to partially occlude blood flow in the aorta, resulting inreduction of blood flow to the spinal cord. A similar technique may beemployed to condition the brain to stimulate production ofneuroprotective agents. To induce cerebral ischemia, the constrictor ispositioned upstream from the takeoff of the innominate artery, orbetween the innominate artery and the left common carotid artery.

It will be understood that there are many advantages in using thepartial aortic occlusion devices and methods disclosed herein. Forexample, the devices can be used (1) to provide variable partialocclusion of a vessel; (2) to augment and maintain cerebral perfusion inpatients suffering from global or focal ischemia; (3) to condition thebrain or spinal cord to secrete neuroprotective agents prior to a majorsurgery which will necessitate reduced cerebral or spinal perfusion; (4)to prolong the therapeutic window in global or focal ischemia; (5) toaccommodate other medical devices, such as an atherectomy catheter; (6)prophylactically by an interventional radiologist, neuroradiologist, orcardiologist in an angiogram or fluoroscopy suite; (7) for prevention ofcerebral ischemia in patients undergoing procedures, such as coronarycatheterization or surgery, where cardiac output might fall as a resultof arrhythmia, myocardial infarction or failure; (8) to treat shock,thereby eliminating or reducing the use of systemic vasoconstrictors;(9) to prevent hypotensive neurologic damage during carotid stenting,and (10) to rescue vasospasm induced by hemorrhage or interventionalprocedures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a patient's systemic arterial circulation relevant tothe present invention.

FIG. 2A illustrates an embodiment of the devices constructed accordingto the present invention for providing partial occlusion of a vessel.

FIG. 2B illustrates another embodiment of the devices constructedaccording to the present invention for providing partial occlusion of avessel.

FIG. 3 illustrates another embodiment of devices having two expandablemembers according to the present invention for providing partialocclusion of a vessel.

FIG. 4 illustrates deployment of the device shown in FIG. 3 in theaorta.

FIG. 5A illustrates a plot of cerebral blood flow and aortic pressure v.percent occlusion area of the descending aorta during use of the devicesconstructed according to the present invention for providing partialocclusion of a vessel.

FIG. 5B illustrates a plot of cerebral blood flow v. time during use ofthe devices constructed according to the present invention for providingpartial occlusion of a vessel.

FIG. 6 illustrates another embodiment of the devices constructedaccording to the present invention for providing partial occlusion of avessel.

FIG. 6A illustrates a cross-sectional view of the device shown in FIG.6.

FIG. 6B illustrates a hypotube with an atraumatic tip.

FIG. 6C illustrates a pig-tailed atraumatic tip for a catheter.

FIG. 6D illustrates a cross-sectional view of an alternative design forthe catheter of FIG. 6.

FIG. 6E illustrates a stylet for use in the present invention.

FIG. 6F illustrates a hypotube having a skive.

FIG. 7 illustrates another embodiment of the devices constructedaccording to the present invention for providing partial view of thedevice shown in FIG. 10 taken through section line B-B.

FIG. 11 illustrates another embodiment of the devices constructedaccording to the present invention having a constricting balloon withcentering mechanism.

FIG. 11A illustrates a cross-section view of the device shown in FIG. 11taken through section line A-A.

FIG. 12 illustrates another embodiment of the devices constructedaccording to the present invention having assorted balloon sizes.

FIG. 13 illustrates another embodiment of the devices constructedaccording to the present invention having a control rod and membranebarrier.

FIG. 13A illustrates the membrane harrier with a minimum (20%)cross-sectional profile,

FIG. 13B illustrates the membrane barrier with an enlarged (40%)cross-sectional profile.

FIG. 13C illustrates the membrane barrier with a further enlarged (60%)cross-sectional profile.

FIG. 13D illustrates the membrane harrier with a further enlarged (80%)cross-sectional profile.

FIG. 14 illustrates another embodiment of the devices constructedaccording to the present occlusion of a vessel.

FIG. 7A illustrates a cross-sectional view of the device shown in FIG.7.

FIG. 8 illustrates another embodiment of the devices constructedaccording to the present invention for providing partial occlusion of avessel.

FIG. 9 illustrates a variable pressure balloon as used in devicesconstructed according to the present invention.

FIG. 10 illustrates another embodiment of the devices constructedaccording to the present invention having a constricting balloon withcentering mechanism.

FIG. 10A illustrates a cross-section view of the device shown in FIG. 10taken through section line A-A.

FIG. 10B illustrates a cross-section invention for providing partialocclusion of a vessel.

FIG. 15 illustrates a constrictor of the device depicted in FIG. 14.

FIG. 16A illustrates an outer conical shell employed in the constrictorof FIG. 15.

FIG. 16B illustrates an inner conical shell employed in the constrictorof FIG. 15.

FIG. 17 illustrates an alternative embodiment of the constrictors ofFIG. 15 having elongate rectangular ports.

FIG. 18 illustrates another embodiment of the occluder having a beveledlip.

FIG. 19 illustrates another embodiment of the occluder having aplurality of graduated rings.

FIG. 20 illustrates complete misalignment of the ports on the outer andinner conical shells.

FIG. 21 illustrates partial alignment of the ports on the outer andinner conical shells.

FIG. 22 illustrates complete alignment of the ports on the outer andinner conical shells.

FIG. 23 illustrates another embodiment of the device for providingpartial occlusion of a vessel.

FIG. 24 illustrates another embodiment of the constrictor employed inthe device of FIG. 23.

FIG. 25A illustrates a frontal view of the constrictor of FIG. 24 havinga plurality of preformed flaps extending perpendicular to thelongitudinal axis of the constrictor.

FIG. 25B illustrates a frontal view of the flaps of FIG. 25A under anexternal force.

FIG. 25C illustrates a frontal view of the constrictor of FIG. 24 havinga plurality of preformed flaps extending parallel to the longitudinalaxis of the constrictor.

FIG. 25D illustrates a frontal view of the flaps of FIG. 25C under anexternal force.

FIG. 26 illustrates another embodiment of the occluder having flapsincluded in the collar of the outer conical shell.

FIG. 27 illustrates still another embodiment of the device for providingpartial occlusion of a vessel.

FIG. 28 illustrates an embodiment of the constrictor employed in thedevice of FIG. 27.

FIG. 29 illustrates the constrictor of FIG. 28, having an inflatedring-shaped balloon for reducing blood flow through a blood conduit.

FIG. 30 illustrates the occluder of FIG. 28, having a deflatedring-shaped balloon.

FIG. 31 illustrates a suction/atherectomy catheter introduced throughthe constrictor of FIG. 28.

FIG. 32 illustrates a perfusion and an EPS catheter introduced throughthe constrictor of FIG. 28.

FIG. 33A illustrates the constrictor of FIG. 15 inserted in the aortadownstream from the left subclavian artery and partially occludingaortic blood flow.

FIG. 33B illustrates the constrictor of FIG. 26 inserted in the aortadownstream from the left subclavian artery and partially occludingaortic blood flow.

FIG. 34 illustrates the constrictor of FIG. 15 inserted in the aortadownstream from the right brachiocephalic artery and partially occludingaortic blood flow.

FIG. 35 illustrates a suction/atherectomy catheter introduced throughthe constrictor of FIG. 15 and inserted in the left carotid arteryproximal to a thromboembolic occlusion.

FIG. 36 illustrates the constrictor of FIG. 15 inserted in the aortaupstream from the lumbar or lumbar or spinal arteries.

FIG. 37 illustrates the constrictor of FIG. 15 inserted in the renalarteries.

FIG. 38 depicts a graph of cerebral blood flow versus time in a strokeinduced rat brain.

FIG. 39 depicts a fluorescent stain of a rat brain section having normalcapillary perfusion.

FIG. 40 depicts a fluorescent stain of the stroke center in a rat brainsection after induction of stroke.

FIG. 41 depicts a fluorescent stain of the stroke penumbra in a ratbrain section after induction of stroke.

FIG. 42 depicts a fluorescent stain of the stroke center in a rat brainsection after placement of a coarctation device.

FIG. 43 depicts a fluorescent stain of the stroke penumbra in a ratbrain section after placement of a coarctation device.

FIG. 44A depicts an embodiment of a constrictor that can be removablymounted on a standard catheter.

FIG. 44B depicts the inflated constrictor of FIG. 44A.

FIG. 44C depicts another embodiment of a constrictor that can beremovably mounted on a standard catheter.

FIG. 44D depicts the inflated constrictor of FIG. 44C.

FIG. 44E depicts another embodiment of the constrictor having amanometer and lumen allowing passage of other devices.

FIG. 44F depicts the inflated constrictor of FIG. 44E.

FIG. 44G depicts another embodiment of the constrictor having a springmechanism constricting its lumen.

FIG. 44H depicts the constrictor of FIG. 44G with the spring mechanismrelaxed.

FIG. 45A depicts a constrictor mechanism mounted on a stent deploymentcatheter.

FIG. 45B depicts the catheter and constrictor of FIG. 45A with theconstrictor expanded.

FIG. 46A depicts another embodiment of a constrictor having anintroducer sheath and an inflatable balloon catheter within the sheath.

FIG. 46B depicts a cross-sectional view of the catheter of FIG. 46Athrough sectional line B-B.

FIG. 47A depicts a mechanism for partial obstruction of the aorta.

FIG. 47B depicts another mechanism for partial obstruction of the aorta.

FIG. 47C depicts another mechanism for partial obstruction of the aorta.

FIG. 47D depicts another mechanism for partial obstruction of the aorta.

FIG. 48 depicts another embodiment of the devices constructed accordingto the present invention for providing partial occlusion of a vessel.

FIG. 48A depicts a cross-sectional view of the catheter of FIG. 48.

FIG. 48B depicts another embodiment of the devices constructed accordingto the present invention for providing partial occlusion of a vessel.

FIG. 48C depicts a cross-sectional view of the catheter of FIG. 48B.

FIG. 48D depicts a guiding catheter for use with the catheter of FIG.48B.

FIG. 48E depicts the guiding catheter of FIG. 48D disposed within thecatheter of FIG. 48B.

FIG. 48F depicts adjustment of the guiding catheter within the catheterof FIG. 48B.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The devices and methods disclosed herein are most useful in treatingpatients suffering from global cerebral ischemia due to systemiccirculatory failure, and focal cerebral ischemia due to thromboembolicocclusion of the cerebral vasculature. However, it will be understoodthat the devices and methods can be used in other medical conditions,such as hypertension and spinal cord conditioning.

Systemic arterial circulation relevant to the methods of the presentinvention is described in FIG. 1. During systole, oxygenated bloodleaving heart 8 enters aorta 10, which includes ascending aorta 12,aortic arch 14, and descending aorta 22. The aortic arch gives rise tobrachiocephalic trunk 16, left common carotid artery 18, and leftsubclavian artery 20. The brachiocephalic trunk branches into rightcommon carotid artery 24 and right subclavian artery 26. The right andleft subclavian arteries, respectively, give rise to right vertebralartery 28 and left vertebral artery 34. The descending aorta gives riseto a multitude of arteries, including lumbar (i.e., spinal) arteries 38,which perfuse the spinal cord, renal arteries 40. Which perfuse thekidneys, and femoral arteries 42, which perfuse the lower extremities.

In one embodiment as shown in FIG. 2A, the obstruction device compriseselongate catheter 102 having a proximal end and a distal end, shown herepositioned within descending aorta 22. The distal end has expandablemember 104, e.g., a balloon. Balloon 104 communicates with inflationlumen 51 through port 105. In another embodiment, depicted in FIG. 2B,ports 111 are included in the surface of catheter 102 to allow bloodflow through the distal end of catheter 102 to pass through the catheterdownstream constrictor 104.

In another embodiment as shown in FIG. 3, the obstruction devicecomprises elongate catheter 102 having a proximal end and a distal end.The distal end has first expandable member 104 and second expandablemember 107, e.g., balloons, and in certain embodiments elongateballoons, mounted and spaced from each other. Balloon 104 communicateswith inflation lumen 51 through port 105. Balloon 107 communicates withinflation lumen 109 through port 52. Balloon 104 and balloon 107 arethus able to be inflated independent of each other, or, in otherembodiments, are inflated from a common inflation lumen.

It will be understood that the constrictor, when implemented as aballoon, can be of any shape that is suitable fix use in the aorta. Anelongate balloon (e.g., balloons 104 and 107 in FIG. 3), elliptical orsausage-shape, is particularly desirable because this shape is morestable within rapidly flowing blood. A spherical balloon (althoughuseful in the disclosed inventions) will tend to rock within the aorta,and rotate and bend the catheter to which it is affixed. The use of anelongate balloon, however, reduces the rocking and rotating within thevessel because this shape effectively eliminates one of the degrees offreedom present with a spherical balloon.

In certain embodiments, the catheter is equipped with blood pressuremeasuring capabilities proximal and/or distal to one or each expandablemember. The blood pressure measuring capabilities may comprise amanometer mounted on the catheter or a channel communicating with atransducer at the proximal end and a port at the distal end of thecatheter. Blood pressure measuring may also be accomplished by use of afiber optic in vivo pressure transducer as described in U.S. Pat. Nos.5,392,117 and 5,202,939, incorporated herein by reference in theirentirety, or a Radi pressure wire as described in U.S. Pat. Nos. Re35,648; 5,085,223; 4,712,566; 4,941,473; 4,744,863; 4,853,669; and4,996,082, incorporated herein by reference in their entirety.

In use, the catheter is inserted in descending aorta 22, and advanced toa position such that first constricting balloon 104 is upstream of therenal arteries, celiac, and superior mesenteric artery, and secondconstricting balloon 107 is downstream of these arteries as shown inFIG. 4. A two-balloon device permits independent regulation andadjustment of cerebral blood flow and renal blood flow. Thus, downstreamballoon 107 is first expanded while measuring cerebral blood flow untilthe desired increase over baseline is obtained, e.g., 100% increase.This step will also result in increased blood flow to the renal andsuperior mesenteric arteries. If this step results in inadequatecerebral blood flow increase, then upstream balloon 104 is expanded toconstrict upstream the renal and superior mesenteric arteries until thedesired cerebral blood flow increase is obtained. Deployment of theupstream constrictor reduces blood flow to the renal and superiormesenteric arteries as compared with blood flow before deployment of theupstream constrictor.

If the deployment of downstream balloon 107 produces the desiredincrease in cerebral blood flow, then upstream balloon 104 will not bedeployed in certain procedures. In other procedures, upstream balloon104 is deployed so that constriction in downstream balloon 107 can bereduced, thereby partially relieving the renal and superior mesentericarteries of increased flow. It will be understood that inclusion of aballoon downstream is desirable in some cases because it allows thesurgeon to maintain renal blood flow at or above baseline whileincreasing blood flow to the brain. It may also be desirable to achieveconstriction predominantly downstream of the renal arteries that supplyblood to kidneys 83 to avoid obstructing the spinal arteries that lieupstream the renal arteries. It may also be desirable to have bothballoons 107 and 104 partially inflated, rather than either balloonfully inflated, to avoid blocking arteries that branch from the aorta.

Alternatively, both balloons may be inflated simultaneously until adesired increase in cerebral flow is achieved. In this manner, flow tothe renal arteries will be maintained at substantially the initialbaseline flow. If it is desired to further adjust renal blood flow whilemaintaining the cerebral blood flow and/or increase in proximal aorticpressure, the two balloons can be simultaneously adjusted, e.g., oneincreased and one decreased, until the desired renal blood flow isachieved.

It will be understood that one objective for the devices and methodsdescribed herein is to increase cerebral blood flow during stroke.Expansion of a constrictor in the descending aorta produces increasedblood pressure upstream of the constrictor, which leads to increasedcerebral blood flow. A small change in upstream blood pressure, however,can produce a very large change in cerebral blood flow. Cerebral bloodflow can be measured by transcranial Doppler, functional MRI, CT scan,PET scan, SPECT scan, or any other suitable technique known in the art.In certain procedures therefore, it may be desirable to adjust expansionof constrictors 107 and/or 104 in response to measured cerebral bloodflow increase instead of or in addition to, measured blood pressureincrease upstream the constrictor and/or measured blood pressuredecrease downstream the constrictor. If cerebral blood flow is to beused as a measure, then a baseline blood flow is measured beforeexpansion of the constrictor. The constrictor is then expanded whilemeasuring blood flow until a desired increase in flow is achieved.Typically, the desired increase will be 50 percent or greater, 60percent or greater, 70 percent or greater, 80 percent or greater, 90percent or greater, or 100 percent or greater of baseline blood flow, ormore than 100 percent. The amount of increased cerebral blood flow willdepend on a variety of factors including the patient's baseline bloodpressure. If the blood pressure is excessively high, it may be desirableto achieve a smaller increase in cerebral blood flow, so as not toincrease the proximal aortic pressure to an excessive value. Inaddition, the increase in the amount of pressure or flow achievable willalso depend on baseline conditions. For example, the lower the baselineaortic pressure, the larger the pressure increase achievable.

A plot of upstream aortic blood pressure and cerebral blood flow versuspercent occlusion of the cross-sectional area of the descending aorta isshown in FIG. 5A. As can be seen from these data generated in a modelsystem, a favorable increase in cerebral blood flow and aortic bloodpressure occurs at 50 percent occlusion and greater, at 56 percentocclusion and greater, and at 64 percent occlusion and greater. An evenmore favorable increase occurs at 71 percent occlusion and greater, 76percent occlusion and greater, and at 83 percent occlusion and greater.A still more favorable increase can be seen at 91 percent occlusion andgreater, 96 percent occlusion and greater, and at 98 percent occlusionand greater.

It will further be understood that, when constriction is applied, thereis a sharp increase in cerebral blood flow. The initial percent increasein cerebral flow is believed to be significantly higher than the percentincrease in upstream aortic pressure in the presence of stroke. Thisappears to be the case for both the ischemic brain and the normal brain.A plot of cerebral blood flow versus time as set forth in FIG. 5B,however, shows that the cerebral blood flow rate decays with time afterthe initial application of the constrictor at time=t1. This decay ispossibly due to autoregulation within the brain. When the constrictionis released, even for a short time (e.g., 10 seconds, 20 seconds, 30seconds, 1 minute, or more), and then applied again (time=t2), there isagain a sharp increase in cerebral blood flow followed by gradual decay.Thus, one contemplated treatment regimen would include periodic (every30 minutes or one hour) release of constriction to “reset” theautoregulatory system followed by re-expansion of the occluder at timet2. Another contemplated treatment regimen would include a gradualincrease in constriction with time in order to maintain an approximatelyconstant rate of increased cerebral blood flow.

The aorta is a curved vessel that bends as it progresses from the aorticarch to the branch at the femoral arteries, as shown in FIG. 4. When oneor both of the occlusion balloons are inflated, the blood pressure inthe aorta upstream of the occluder(s) is caused to increase, while thepressure below the occluder(s) is decreased from baseline. Withsignificant obstruction, e.g., 85-95 percent diameter obstruction, thispressure drop along the length of the occlusion balloon(s) can besignificant, on the order of 20-150 mmHg. This pressure drop, by actingon the cross-sectional area of the occlusion balloon(s) creates asubstantial longitudinally directed compressive force on the shaft ofthe catheter. The pressure drop and force are pulsatile in nature (dueto systole and diastole) and tend to pulsatilly push the occlusiondevice down and back up.

To minimize this motion it is desirable to reinforce the catheter shaft.One way to reinforce the shaft is to incorporate stiffening mandrel orstylet 240. This may be incorporated within the shaft at the point ofmanufacture or it may be introduced within the shaft once the occlusiondevice is positioned in the aorta. Furthermore, the mandrel or stylet240 may be a solid wire, or may be a hollow tube, such as a hypotube.

In use, a guidewire is advanced into the aorta. Catheter 102 is advancedover the guidewire. Once the catheter is in place, the guidewire isremoved and mandrel 240 is advanced into a lumen of the catheter untilit reaches the proper position. In certain procedures, the mandrel has acurvature at the end to forcibly deflect the occlusion balloon(s) to thewall of the aorta. The mandrel is then periodically rotated toreposition constrictors 104 and 107 at a new location along the lumenalwall of aorta 22. This periodic movement ensures that branching vesselsare not deprived of blood for too long.

Although the balloon(s) of this embodiment will tend to be deflected tothe wall of the aorta, the mandrel will further assure that the balloonwill be deflected, resulting in an eccentric annular flow path for theballoon. Although an eccentric annulus has less flow resistance than aconcentric annulus, it is desirable to prevent this non-centeringembodiment from periodically becoming centered, as this would allow theflow resistance to vary over time.

A further dual balloon device is illustrated in FIG. 6. Distal balloon104 and proximal balloon 107 are both fabricated of an elastomericmaterial such as blow molded polyurethane. Both are preferably molded tohave an initial inflated diameter of about 10 mm, with a capability ofbeing inflated to 25 mm with increasing pressure. It is anticipated thatother sizes could be utilized. For example, the distal balloon could belarger than the proximal balloon, with an initial diameter of 15 mm, anda capability of being inflated to 35 mm with increasing pressure.

Both balloons may have a body length of from 3-6 cm, preferably about 4cm. The distal tapered cone 113 and proximal tapered cone 115 may have alength of 1-3 cm, and about 2 cm. Each balloon has two cylindricalwaists 117 and 119 which are used in the securing of the balloons tocatheter shaft 102. The balloons may be adhesively bonded to thecatheter shaft, or may be thermally bonded. Other suitable means ofjoining the balloons are also contemplated.

The balloons 104 and 107 are mounted on the distal region of cathetershaft 102. In this embodiment, the catheter shaft structure includes aunitary extruded multi-lumen tube (see cross-section in FIG. 6A), whichextends for the full length of the device, with the exception of a softtip attached at the distal end. The multi-lumen tube is preferablyformed of an extrudable polymer, such as Pebax, polyethylene,polyurethane, polypropylene, or nylon. Alternatively, the shaftstructure could be fabricated as illustrated in FIG. 6D. In thisstructure, individual thin walled tubes are used to define each lumen,and are preferably formed of a material suitable for very thin walls,such as polyimide or polyimide composite structures. As illustrated, theinter-balloon pressure monitoring lumen 161, and the inflation lumens 51and 109 are defined by thin polyimide tubes, and the wire lumen isdefined by a thin wailed composite tube of PTFE, braided metal, andpolyimide. The four thin walled tubes 51, 109, 161, and 162 are thenencased within an extrusion or coating 163 of a polymeric material, suchas Pebax, polyurethane, polyethylene, or other suitable polymer.

There are four lumens within tube 102, wire lumen 162, inter-balloonpressure monitoring lumen 161, and two inflation lumens 51 and 109, oneeach for delivery of inflation fluid to each balloon. Each balloon isinflated via ports 52 and 105 which allow fluid communication betweenthe inflation lumen and the balloon interior. The portion of theinflation lumens which extend distally of their respective ports areoccluded by suitable means such as an adhesive plug.

The inter-balloon pressure monitoring lumen 161 is in fluidcommunication with the surrounding blood via a port 160 in the tubingwall. When a suitable fluid such as saline resides in this lumen duringused of the device, the blood pressure at the port is transmitted downthe lumen to a pressure transducer. When the device is positioned aspreferred, with the two balloons spanning the renal arteries, the renalblood pressure can be monitored, providing input to influence the degreeof balloon inflation of the two balloons.

Wire lumen 162 is used during initial placement with a guide wire, whichmay be later removed, or may be left in place. The remaining spacewithin the wire lumen may be used to monitor the blood pressure upstreamfrom distal balloon 104. This is another input which may be used toinfluence the degree of inflation of one or both balloons.

Preferred tubing dimensions for the inflation lumens are between 9 and60 mils, more preferably between 1 and 2.0 mils. Preferred tubingdimensions for the pressure lumens are between 5 and 60 mils, morepreferably between 8 and 20 mils. Preferred tubing dimensions for themain lumens are between 30 and 80 mils, more preferably between 35 and60 mils.

As mentioned, the shaft structure also includes a soft tip. Preferably,this is a single lumen tube fabricated of a more flexible material thanthat of the multi-lumen tubing. The tip is attached to the distal end ofthe multi-lumen tube by suitable means such as a thermal or adhesivebutt joint. The single lumen within the tip creates an extension of thewire lumen. The soft tip is preferably about 2 to 10 cm long, and servesas an atraumatic tip facilitating catheter introduction and positioning,as well as providing an atraumatic “bumper” to the device during longterm indwelling use. The tip may be straight, and may further include atapering dimension on the outer and inner diameters. The tip may also befabricated in a “pigtail” shape (FIG. 6C), which straightens in thepresence of a guide wire extending through the wire lumen, but returnsto the curled shape upon removal of the guide wire. A pigtail shape isrelatively atraumatic.

The device as described is relatively flexible for smooth advancementover a guidewire, and may be introduced into the aorta without the needfor fluoroscopic guidance. Radio-opaque markers would nonethelesspreferably be provided, in the instances where fluoroscopic guidance isutilized, or if a simple plate x-ray is used to assist in devicepositioning.

As mentioned previously, when one or both balloons of a dual balloondevice are inflated, significant longitudinal compressive forces can beimposed on the catheter. To help stabilize the device, the shaftstructure of this embodiment provides for subsequent introduction of astiffening element, such as a wire stylet, or a hypotube. If a wirestylet is used, the initial delivery guidewire is removed, to make roomfor the stylet. The stylet (FIG. 6E) is preferably tapered, and has abulbous tip, facilitating smooth introduction into the wire lumen. Thestylet may be quite large, occupying most of the available lumen.However, it is preferable to still maintain a clearance between thestylet and the wall of the wire lumen, to maintain the ability tomonitor blood pressure. Alternately, the stylet may incorporate apressure transducer mounted near the tip, in which case, the wire lumencan be fully occupied by the stylet.

If a hypotube is used as the stiffening element, the initial guide wireneed not be removed, as long as the inner diameter of the hypotube islarge enough to accommodate the guide wire, which is typically either0.035 or 0.038 inches in diameter. Preferably, the hypotube has adiameter slightly less than the wire lumen diameter, and a taperingouter diameter toward the distal end, to facilitate smooth tracking inthe wire lumen. Hypotube 165 (FIG. 6F) can further incorporate a “skive”to gain further flexibility near the distal end to facilitate smoothtracking. Alternately, the distal portion of the hypotube can have ahelical cut of progressively tighter pitch (FIG. 6B), or other patternsof removed material in hypotube 165 to facilitate a gradually increasingflexibility. The inner lumen of the hypotube can be used as a pressuremonitoring lumen for the upstream aortic pressure. Preferably thehypotube is coated both on the internal surface by a lubricious andnon-thrombogenic material, such as a hydrophilic coating, PTFE liner, ora paralene coating. With both the wire stylet and the hypotubestiffening elements, it is contemplated that they could be incorporatedinitially within the device, as opposed to introduced subsequent topositioning of the balloons. If the stiffening element is initiallyincorporated into the shaft structure, it is preferred to connectsomewhere in the distal region of the hypotube to the shaft tube, bysuitable means such as an adhesive or thermal bonding.

Referring again to FIG. 6, at the proximal end of the device, a manifoldstructure is connected to the shaft structure. The manifold structureincludes luer fittings that communicate with each of the lumens. Fitting169 communicates with pressure monitoring lumen 161, fitting 167communicates with proximal balloon inflation lumen 109, and fitting 168communicates with distal balloon inflation lumen 51. The entire shaftstructure and balloons are preferably coated with a non-thrombogeniccoating, such as a hydrophilic coating, and/or a heparin coating. Otheranti-thrombogenic agents are also possible, such as phospholcholine.

FIG. 7 illustrates an additional embodiment for a dual balloon occlusiondevice, and utilizes an alternative shaft structure. The shaft structurecomprises two primary components—multi-lumen polymeric tube 102, andhypotube 165. The hypotube in this embodiment is fabricated directlyinto the device. The multi-lumen tube has three lumens, as shown in FIG.7A. The main lumen 162 is circular. The hypotube resides within thislumen, and the remaining leftover annular space 105 serves as theinflation lumen for the distal balloon. Lumen 109 serves as the lumenfor inflation of the proximal balloon, and lumen 161 serves as the lumenused in connection with inter-balloon pressure monitoring.

Hypotube 165 extends distally of the multi-lumen tube, and preferablyterminates distal of the distal balloon. The hypotube is preferablylined on the inner surface, in a manner as described for the hypotubeabove. The lumen of the hypotube serves as the guide wire lumen as wellas the pressure monitoring lumen for the upstream aortic pressure. Thedistal balloon is attached to the exterior of hypotube 165 by suitablemeans such as adhesive or thermal bonding. The distal end of thehypotube can incorporate features as described above to serve as atransition in stiffness. A soft tubular tip is preferably attached tothe hypotube, creating an atraumatic tip.

FIG. 8 illustrates another embodiment of a dual balloon occlusiondevice, which utilizes an alternative shaft structure. The shaftstructure is comprised of three coaxially positioned tubular components.Outer tube 102 is circular and polymeric, and defines lumen 52 which isused for inflation of proximal balloon 107. Middle tube 170 is circularand polymeric and defines lumen 105 which is used for inflation ofdistal balloon 104. Inner tube 165 is circular, and preferably ahypotube. The tubes are arranged such that proximal balloon 107 isattached proximally to outer tube 102, and distally to middle tube 170.The distal balloon is attached proximally to middle tube 170, anddistally to inner tube 165.

Hypotube 165 defines lumen 171 which serves as a guide wire lumen, aswell as a lumen for monitoring the upstream aortic blood pressure. Thehypotube is preferably lined on the inner surface, in a manner asdescribed for the hypotube above. The distal end of the hypotube canincorporate features as described above to serve as a transition instiffness. A soft tubular tip is preferably attached to the hypotube,creating an atraumatic tip. As with the above embodiments, the entireshaft structure and balloons are preferably coated with anon-thrombogenic coating, such as a hydrophilic coating, and/or aheparin coating. Other anti-thrombogenic agents are also possible, suchas phospholcholine.

The balloon constrictors described herein are desirably blow molded froma material that is elastomeric, such as polyurethane, allowing anadjustable balloon diameter, as indicated in FIG. 9. The balloons willtypically be sized to achieve full expansion, i.e., wrinkle-freeexpansion, at approximately 10 mm diameter in cross-section and at apressure of 0.5-5 psi. A pressure of 5 psi at the low end of theoperating range is desirable because the balloon is firm at thispressure and therefore resists the tendency to distort its geometry in arapidly flowing blood stream. The balloon material will allow furtherexpansion (beyond 10 mm) upon farther inflation (e.g., by syringe) to amaximum diameter of approximately 25 mm and at a pressure of 12-50 psi.An operating range of approximately 10-25 mm balloon diameter isdesirable to accommodate variations in patient anatomy and to allow thesurgeon to vary constriction to adjust cerebral blood flow rate to thedesired level. For larger aortas, a balloon of 15-30 mm may bedesirable. A wrinkle-free balloon at 10 mm diameter cross-section isdesired because wrinkles will produce unpredictable and variable flowproperties, and wrinkles will produce a distortion in balloon materialwith material bundling together at the downstream edge of the balloon.

In other embodiments as depicted in FIG. 10, a centering mechanism willbe used to maintain the constricting balloon apart from the vessel wall.Catheter 102 includes balloon 107, and inner sheath 53 includes balloon104. The centering mechanism for balloon 107 here is provided by, struts63 mounted (either slideably or fixedly) at a proximal end to catheter102, and at a distal end to inner tube 53. The centering mechanism forballoon 104 is provided by struts 62 mounted (either slideably orfixedly) at a proximal end to inner tube 53, and at a distal end toinner tube 53. A cross-section taken through section line A-A is shownin FIG. 10A, and a cross-section taken through section line B-B is shownin FIG. 10B. Alternative structures, such as a braid as a centeringmechanism, are also contemplated.

An alternative centering mechanism is shown in FIG. 11. Catheter 102includes inner shaft 65 having a working channel. Constricting balloon104 is bonded to shaft 65 at a distal end thereof. Self-expanding wires66 are bonded at one end to catheter 102, and at a second end tocentering mechanism 64. Here, centering mechanism 64 is a deployablewire mesh with fabric or polymer cover. A cross-section taken throughsection line A-A is shown in FIG. 11A. Wire mesh 64 is surrounded bycover 67. Distal supporting struts 68 are provided to strengthen thecentering mechanism distally.

By maintaining the constricting balloon centered in the vessel, bloodflows around the balloon on all sides. Thus, all branching vessels areperfused when this design is employed. Moreover, the velocity of bloodflow increases in the region of the constrictor. This increased velocityin combination with the balloon channeling blood against the vessel wallcan actually increase perfusion of branching vessels in certain cases,it will be understood that, in the absence of a centering mechanism andwithout a mandrill, the catheter and the one or more balloons willcontact and bear against the lumenal wall of the aorta.

In another embodiment as shown in FIG. 12, catheter 102 carriesslideable inner shaft 53. Shaft 53 includes an inflation lumen and anassortment of constricting balloons 104 mounted at different positions.Each of these balloons has a different diameter of expansion toaccommodate different degrees of constriction and different patientanatomy. In use, the first and smallest balloon is advanced from thedistal port of catheter 102 and deployed. If a larger balloon is needed,then the second, larger balloon is advanced out of the catheter anddeployed. If needed, the third balloon can be advanced into the vesseland deployed. At the proximal end of catheter 102 is outer sheath 75 andY-adapter 55 with inflation deflation port 81 and port 82 for aguidewire, for flushing, or for access by any other tools orinstruments. Y-adapter 55 is connected to sheath 75 by hub 83 that hascapabilities for multiple position adjustment.

FIG. 13 depicts occlusion membrane 76 that acts as an occluding memberinstead of using a balloon. Occlusion membrane 76 comprises a coatedmesh. Catheter 102, having a flexible outer sheath, carries control rod77. The distal end of control rod 77 is fixed to occlusion membrane 76at its distal end. When control rod 77 is extended, occlusion membrane76 is stretched as shown in FIG. 13, reducing the cross-sectionalprofile at the proximal end of occlusion membrane 76. As control rod 77is withdrawn, occlusion membrane 76 progressively expands, increasingthe cross-sectional profile at the proximal end as shown in FIGS. 13B,13C, and 13D. At the proximal end, control rod 77 terminates inpositioning handle 78 for adjusting the cross-sectional profile of theocclusion membrane 76.

FIG. 14 depicts occlusion catheter 100 for use in the methods describedherein. The device includes elongate catheter 102, distally mountedexpandable constrictor, i.e., occluder, 104 having distal opening 124and variable flow mechanism 108. The constrictor, when expanded, hasmaximum periphery 110, which conforms to the inner wall of a vessel toform a secure seal with the vascular wall, such that blood flow throughthe vessel can be effectively controlled. Opening 124 receives bloodfrom distal the constrictor and controls the passage of blood proximalthe constrictor. Variable flow mechanism 108, connected to rotary unit150, operates the constrictor, thereby controlling (1) the flow ratethrough the occlusion, and (2) upstream blood pressure. Preferably, thedevice includes manometer 112, which is connected to pressure monitor156 and pressure limiter 114. Rotary unit 150 receives blood pressuremeasurements from the manometer. Pressure limiter 114, connected to therotary unit and the pressure monitor, prevents the upstream anddownstream blood pressure from exceeding, respectively, a set maximumand minimum pressure differential. A proximal end of the catheter isequipped with adapter 103, from which pull wires 132 can be manipulatedfor collapsing the occluder and to which the rotary unit, pressuremonitor, and/or pressure limiter can be connected.

Referring to FIG. 15, the occlusion device comprises catheter 102 andconstrictor 104. The catheter is constructed from a biocompatible andflexible material, e.g., polyurethane, polyvinyl chloride, polyethylene,nylon, etc. The catheter includes lumen 116 through which variousoperative elements pass. Alternatively, the catheter may include morethan one lumen to support various operative elements. The catheter alsoincludes proximal adapter 103 (see FIG. 14), which provides an interfacebetween the catheter and the various instruments received by thecatheter. The occluding mechanism consists of outer conical shell 118and inner conical shell 136, each having a distal open base and aproximal apex. Pre-shaped ring 130 is affixed to base 120 of the outershell to facilitate expansion of the constrictor. The ring is formed ofa resilient material, capable of expanding the occluder to achieve amaximum periphery, which is defined by the outer circumference of thering. Ring 130 may, in certain embodiments, further include an anchoringmechanism, such as hooks, bonded to the outer circumference of the ring.Expansion of the ring causes the grasping structure to engage thesurface of the vessel wall, thereby securing the occluder and preventingdisplacement in the vessel due to force exerted by blood flow. In otherembodiments, the anchoring is provided by an adhesive strip, vacuum, ormerely by frictional engagement of the vessel lumen by the ring.

The constrictor can be collapsed to facilitate insertion into andremoval from a vessel. A plurality of pull wires 132 (FIG. 14) aredisposed within torque cable 148, and are distally connected to base 120of outer shell 118 and proximally passes through adapter 103. Theconstrictor is collapsed by applying a tensile force on wires 132, usingtorque cable 148 to provide leverage to the pull wires, thereby drawingthe circumference of the open base 120 towards its center and collapsingthe &cinder. A guide sheath (not shown) can be alternatively used tocollapse the constrictor. Using this technique, the guide sheath wouldcover the constrictor and be withdrawn to release the constrictor andadvanced to collapse the constrictor.

Opening 124 is formed in base 138 and 120 of the respective inner andouter conical shells to provide an inlet for blood flow. Conicalinterior 106 communicates with ports 128 of the outer shell. When theconstrictor is deployed, blood flows into opening 124, through interior106, and exits through ports 128. The occluding mechanism comprisesinner conical shell 136 (partially shown in phantom in FIG. 15), whichis rotatably disposed within outer shell 118 as shown in FIGS. 8, 9, and10. The inner shell can be rotated relative to the outer shell throughtorque cable 148, which is disposed in lumen 116 of catheter 102.

Manometer 112 comprises upstream pressure tube 152 and downstreampressure tube 154, both connected proximally to a pressure monitor toprovide respective blood pressure measurements upstream and downstreamthe constrictor. The upstream pressure tube extends distal to opening124, or may be attached to the inner shell. The downstream pressure tubeextends through an orifice in the catheter proximal to the constrictor.The upstream and downstream blood pressure measurements are recorded anddisplayed by the pressure monitor at a proximal end of the catheter. Apressure limiter, programmed with a maximum pressure threshold to limitthe upstream blood pressure and a minimum pressure threshold to limitthe downstream blood pressure, is connected to the pressure monitor toreceive pressure measurements therefrom, and transmits information to arotary unit. The limiter thereby prevents the rotary unit from, rotatingthe inner shell relative to the outer shell in a manner that would causethe upstream blood pressure to exceed the maximum threshold, or thedownstream blood pressure to fall below the minimum threshold. Withoutthe rotary unit, torque cable 148 can also be manually rotated to obtaindesired upstream and downstream blood pressures. An audible alarm may beincorporated into the pressure limiter to sound when blood pressuresexceeds the thresholds. The pressure limiter may further comprise aninterlocking device. The interlocking device, in operative associationwith upstream and downstream tubes 152 and 154, can lock inner shell 136with respect to outer shell 118 as blood pressures approach the setthresholds. It should be noted that although the rotary unit, pressuremonitor, and pressure limiter are shown as separate units, they may beincorporated into an integral unit.

Referring to FIGS. 16A and 16B, the expanded constrictor comprises outerconical shell 118 having base 120 and apex 122, and inner conical shell136 having base 138 and apex 140. The constrictor is preferably composedof a biocompatible material coated with heparin to prevent bloodclotting. The conical shape of the expanded constrictor minimizesturbulence caused by placement of the occluder in the vessel. The outerand inner shells include 2, 3, 4, 5, 6, or any other number of ports 128and 144, respectively, in communication with the conical interior topermit blood flow through the occluder. The inner shell can be rotatedrelative to the outer shell, so that ports 144 communicate with ports128. Apices 122 and 140 of the respective outer and inner shells furthercomprise collar 126 and 142. The collars may include engaging threads,so that collar 142 can be inserted and secured into collar 126, andbonded to a distal end of the torque cable, such that the inner shell iscoupled to and rotates with the torque cable. A rotary unit, preferablyincluding a stepper motor (not shown), may be mechanically coupled to aproximal end of the torque cable to provide precise rotational positionof the inner shell relative to the outer shell, thereby providingvariable flow through the occluder.

Instead of having the circular ports in the inner and outer shells asdepicted in FIGS. 16A and 16B, the constrictor may include 2, 3, 4, 5,6, or any other number of ports having other suitable geometric shapes.FIG. 17 depicts constrictor 104 having a plurality of ports constructedas elongate rectangular slots 175.

FIG. 18 depicts another embodiment of the constrictor, which comprisesbeveled lip 140 having distal end 142 and proximal end 141. The proximalend is affixed to base 120 of the outer conical shell. The proximal endhas a larger diameter than the distal end and is everted to prevent theconstrictor from being displaced in the direction of blood flow, therebysecuring the constrictor in the vessel.

Still another embodiment of the occluder may include 1, 2, 3, 4, 5, orany other number of graduated inflatable rings. In FIG. 19, ring 151 isaffixed to the base of the conical shell. Ring 153, having the smallestinflated diameter, is attached to ring 152, which is then attached toring 151, having the largest inflatable diameter. The fully inflatedrings will have a thickness of approximately 2 to 3 millimeters. Similarto the beveled lip of FIG. 20, the rings prevent the outer conical shellfrom being displaced in the direction of blood flow, thereby securingthe constrictor in the vessel.

The flow rate of blood through the constrictor can be easily controlledby rotating inner conical shell 136 (shown with dotted lines) relativeto outer conical shell 118 as depicted in FIGS. 20, 21, and 22. In FIG.20, the inner shell is rotated so that ports 144 and 128 are completelymisaligned, thereby achieving no flow through the ports and completevascular occlusion distally. An the inner shell is rotated clockwiserelative to the second shell in FIG. 21, ports 144 on the inner shellbecome partially aligned with ports 12$ on the outer shell, therebyachieving partial flow through the ports and partial vascular occlusion.In FIG. 22, with continuing clockwise rotation of the inner shell, ports144 become completely aligned with ports 128, thereby achieving maximumflow through the ports. To provide a broader and more predictable rangeof blood flow through the conduit, the ports of the inner and outershells are preferably of equal size and number such that they may alignwith each other.

FIG. 23 depicts another embodiment of the occlusion device for partialocclusion of blood flow in a vessel. Device 200 comprises elongatecatheter 202, distally mounted expandable constrictor 204 with maximumperiphery 210, opening 224, and variable flow mechanism 208 operativelyassociated with the constrictor. The catheter includes adapter 203 atits proximal end. Preferably, the device includes manometer 212 andpressure limiter 214, and pressure monitor 240. The pressure monitorrecords and displays blood pressure data received from the manometer.Longitudinal positioning unit 208, receiving signals from pressurelimiter 214, and controls variable flow mechanism 208 to providevariable blood flow through the constrictor.

Referring to FIG. 24, catheter 202 includes lumen 216. Constrictor 204comprises hollow conical shell 218 having base 220 and apex 222. Theinner circumference of the base forms opening 224, which provides adistal inlet for blood flow through the constrictor. The innercircumference of apex 222 forms collar 228 with proximal opening 226,which provide an outlet for blood flow through the constrictor. Theconical interior, disposed within shell 218, communicates with opening224 distally and opening 226 proximally. When the base of theconstrictor is positioned upstream in a vessel, blood flows into opening224, through the conical interior and exits downstream through opening226. The catheter is bonded to collar 228 about a portion of its innercircumference. The constrictor is expanded by operation of ring 230, abeveled lip, or a series of graduated toroidal balloons as describedabove. The constrictor is collapsed and may be delivered to a vessellocation by using a guide sheath.

The manometer comprises upstream pressure tube 236 and downstreampressure tube 238, which are disposed in lumen 216 of the catheter andconnected proximally to a pressure monitor. The upstream pressure tubeextends distal from the constrictor or may be bonded to the innersurface of the conical shell, thereby providing upstream blood pressuremeasurement. The downstream pressure tube extends through an orifice inthe catheter proximal to the constrictor, thereby providing downstreamblood pressure measurement.

The variable flow mechanism comprises a plurality of flaps 230 pivotallyaffixed to base 220. The flaps are preferably made of a resilientmaterial, such as Nitinol, to resist movement caused by blood flowthrough the conduit. A plurality of pull wires 232, disposed throughlumen 216, are distally connected to flaps 230, such that applying atensile force to the wires pivotally displaces flaps 230 from theirpreformed position. Three of the flaps (shown in dotted lines) aredisplaced inward. Releasing the wires allows the resilient flaps torelax and return to their preformed position. The pull wires are coupledproximally to the longitudinal positioning unit, which provides precisedisplacement of the flaps relative to opening 224. Alternatively, wires232 can be manually tensed to operate the flaps. The pressure limiterreceives pressure measurements from the pressure monitor and transmitssignals to the longitudinal positioning unit to prevent the upstream anddownstream blood pressures from exceeding the set thresholds.

FIGS. 25A, 25B, 25C, and 25D depict frontal views of the constrictorhaving flaps in various positions for controlling blood flow. In FIG.25A, preformed flaps 230 extend radially inward toward the longitudinalaxis of the catheter, as in the absence of a displacing force, i.e., anexternal force other than that created by blood flow. When theconstrictor is positioned in the descending aorta, for example, the sizeof opening 224 and blood flow through the opening is minimized, therebyproviding maximal aortic occlusion. In the presence of a displacingforce, such as pulling the wires to displace flaps 230 from theirpreformed position as depicted in FIG. 25B, the size of aperture 224 andblood flow through the conduit increases, thereby providing partialaortic occlusion.

Alternatively, preformed flaps 230 extend parallel to the longitudinalaxis of opening 224 in the absence of a displacing force as depicted inFIG. 25C. The size of opening 224 and blood flow through the conduit aremaximized, thereby providing minimal blood flow occlusion. In thepresence of a displacing force, flaps 230 are pivotally displaced fromtheir preformed position as depicted in FIG. 25D. The size of opening224 and blood flow through the opening are minimized, thereby providingmaximal blood flow occlusion. Thus, by pivotally displacing flaps 230relative to opening 224, the size of the opening and flow rate throughthe constrictor is controlled to provide variable vessel occlusion.

The constrictor shown in FIG. 24 can be alternatively mounted oncatheter 202, such that base 220 is proximal to apex 222 as shown inFIG. 26. In this embodiment, flaps 230 are formed on open apex 222. Whenconstrictor 204 is inserted downstream in the aorta, for example,pressure tube 238 extends distally from opening 226 to providedownstream blood pressure measurements, whereas pressure tube 236extends proximally through an orifice in the catheter to provideupstream blood pressure measurements.

In FIG. 27, another embodiment of the device comprises catheter 302, adistally mounted occluder 304 with maximum periphery 310, blood passage306 disposed within the constrictor, and variable flow mechanism 308 inoperative association with the blood conduit. Inflation device 334communicates with the constrictor, and inflation device 338 communicateswith the variable flow mechanism. The device preferably includesproximal adapter 303, manometer 312, and pressure limiter 314. Pressuremonitor 312 records and displays blood pressure data from the manometer.The pressure limiter is connected to the pressure monitor and to aninterlocking valve on inflation device 338, such that the blood pressureupstream and downstream the constrictor can be controlled to preventfrom exceeding set thresholds.

Referring to FIG. 28, constrictor 304 is mounted to a distal end ofcatheter 302 having lumen 316. The constrictor comprises a sleeve orcylindrical balloon 318 having outer wall 320 and inner wall 322, whichenclose chamber 323. The cylindrical balloon, has first end 324 withopening 328 and second end 326 with opening 330. Catheter 302 is bondedto inner wall 322 of the cylindrical balloon. Inflation tube 332, housedwithin lumen 316 of the catheter, communicates distally with thecylindrical balloon and proximally with a syringe or other inflationdevice. The cylindrical balloon can be expanded or collapsed byinjecting or removing air, saline, or other medium. Occlusion isprovided by toroidal balloon 334 disposed about the outer or innersurface of sleeve 318 and communicating with inflation tube 336 and asyringe. The inflation device may include an interlocking valve toprevent unintended deflation.

Lumen 306 communicates with opening 328 distally and opening 328proximally. When deployed in a vessel, blood flows through lumen 306 andexits downstream opening 330. The constrictor may further include ananchoring structure, shown in FIG. 28 as rings 333, which are disposedabout outer wall 320 of the cylindrical sleeve and define maximumperiphery 310 of the occluder.

Manometer 312 comprises upstream pressure tube 340 and downstreampressure tube 342, which are operatively connected proximally to apressure monitor. Pressure tube 340 is bonded to the lumen of thecylindrical balloon and extends distal to provide upstream bloodpressure measurements, while tube 342 emerges from the catheter proximalthe occluder to provide downstream blood pressure measurements.

In FIG. 29, fluid is injected to expand balloon 334, therebyconstricting sleeve 318. As a result, blood flow is constricted. In FIG.30, balloon deflation allows sleeve 318 to revert back to its pre-shapedgeometry, increasing blood flow therethrough. Thus, balloon 334 can beinflated and deflated to vary the cross-sectional diameter of lumen 306to vary flow rate.

The occlusion devices described herein can be employed with a variety oftherapeutic catheters to treat vascular abnormalities. For example, asdepicted in FIG. 31, suction/atherectomy catheter 402 can be insertedthrough lumen 306, such that the suction/atherectomy catheter isindependently movable relative to occlusive device 300. Catheter 402includes elongate tube 404 and distally located aspiration port 406,cutting device 408, and balloon 410 for removing thromboembolic materialin a vessel.

In FIG. 32, infusion catheter 502 and EPS catheter 504 are insertedthrough opening 206 of occlusion device 200, such that catheter 502 and504 are independently movable relative to occlusion device 200. Theinfusion catheter, which includes elongate tube 506, distally locatedperfusion port 508, and expandable balloon 510, can be used to removethromboembolic material in a vessel. EPS catheter 504, which includeselongate tube 512 and distally located ablation device 514, may be usedto map out or ablate an extra conduction pathway in the myocardialtissue, e.g., in patients suffering from Wolff-Parkinson-White syndrome.The occlusion device, capable of augmenting cerebral perfusion, istherefore useful not only in facilitating definitive treatment but alsoin cerebral ischemia prevention during EPS and other cardiacinterventions or cardiac surgery, such as coronary catheterization,where sudden fall in cerebral blood flow may occur due to arrhythmia,myocardial infarction, or congestive heart failure.

Referring to FIG. 33A, occlusion device 100 described above can be usedto partially occlude blood flow in aorta 10 of a patient suffering fromglobal cerebral ischemia due to, e.g., septic shock, congestive heartfailure, or cardiac arrest. Constrictor 104 can be introduced in itscollapsed geometry through an incision on a peripheral artery, such asthe femoral, subclavian, axillary, or radial artery, into the patient'saorta. A guide wire may first be introduced over a needle, and thecollapsed constrictor is then passed over the guide wire and the needleto position distal to the takeoff of left subclavian artery 20 in thedescending aorta. The constrictor is expanded, such that maximumperiphery 110 of the occluder, formed by expandable ring 130, sealinglycontacts the inner aortic wall. The position and orientation of thecollapsed or expanded device can be checked by TEE, TTE, aortic archcutaneous ultrasound in the emergency room, or IVUS and angiography inthe angiogram suite.

The expanded constrictor is maintained during systole, during diastole,or during systole and diastole, during which blood distal to thebrachiocephalic artery is forced to pass through opening 106, therebyproviding a continuous partial occlusion of aortic blood flow.Alternatively, partial occlusion of aortic blood flow can beintermittent. As a result, blood flow to the descending aorta ispartially diverted to brachiocephalic artery 16, left subclavian artery20, and left carotid artery 18, thereby augmenting blood flow to thecerebral vasculature. In treating global ischemia, such as in shock,cerebral perfusion is increased by increasing blood flow through bothcarotid and vertebral arteries. Additionally, blood flow to the aorta ispartially diverted to the coronary arteries by using the occlusiondevice, thereby augmenting flow to the coronary arteries. Using thepartial occlusion methods during systemic circulatory failure may,therefore, improve cardiac performance and organ perfusion. Byselectively increasing cerebral and coronary blood flow in this manner,the dosage of commonly used systemic vasoconstrictors, such as dopamineand norepinephrine, may be reduced or eliminated.

Alternatively, the device of FIG. 26, much like the device used toextinguish the flame of a candle, can be introduced through an incisionon left subclavian artery 36 as depicted in FIG. 33B. Constrictor 204 isinserted in aorta 22 distal to the takeoff of the left subclavian arteryto provide partial, variable, and/or continuous aortic occlusion and isadvanced antegrade into the descending aorta. This device isparticularly useful in situations where peripheral incision cannot bemade on the femoral arteries due to arteriosclerosis, thrombosis,aneurysm, or stenosis. The device may alternatively be inserted into theleft or right brachial, left or right subclavian, left or right radialarteries, and then advanced into the aorta. It will be understood thatthese alternative approaches do not require a stiffening mandrel becausethe device is under tension rather than compressive loading. Any of thedevices described herein can be used in these alternative approaches.These alternative approaches may also permit devices that are moreflexible and smaller in diameter.

The devices and methods described in FIGS. 33A and 33B are useful intreating stroke patients within few minutes of stroke symptom, and thetreatment can be continued up to 96 hours or more. For example, intreating focal ischemia due to a thromboembolic occlusion in the rightinternal carotid artery the constrictor may be position distal to thetakeoff of the left subclavian. As a result, blood flow is diverted tobrachiocephalic artery 16 and left CCA to augment both ipsilateral andcontralateral collateral circulation by reversing direction of flowacross the Circle of Willis, i.e., increasing flow in the right externalcarotid artery and left common carotid artery. The collateral cerebralcirculation is further described in details in U.S. Pat. No. 6,165,199,incorporated herein by reference.

In treating focal ischemia due to a thromboembolic occlusion in the leftinternal carotid artery, for example, the constrictor can be positionedproximal to the takeoff of left carotid artery 18 and distal to thetakeoff of brachiocephalic artery 16 as shown in FIG. 34. Contralateralcollateral enhancement is provided by increasing flow through thebrachiocephalic artery, thereby reversing blood flow in the rightposterior communicating artery, right PCA, left posterior communicatingartery 68 and anterior communicating artery, resulting in increasedperfusion to the ischemic area distal to the occlusion and minimizingneurological deficits. Alternatively, the constrictor may be positioneddistal to the takeoff of the left subclavian artery to provide bothipsilateral and contralateral collateral augmentation. Ipsilateralcirculation is enhanced by increasing flow through the left externalcarotid artery and reversing flow along the left ophthalmic artery, bothof which contribute to increased flow in the left ICA distal to theocclusion.

As a result of partially occluding aortic blood flow, blood pressuredistal to the aortic occlusion may decrease, and this may result in areduction in renal output. Blood pressure proximal the aortic occlusionwill increase and may result in excessive rostral hypertension. Theblood pressures, measured by the manometer, are monitored continuously,and based on this information the occlusion is adjusted to avoidperipheral organ damage. After resolution of the cerebral ischemia, theconstrictor is collapsed and removed, thereby removing the aorticocclusion and restoring normal blood flow in the aorta.

In FIG. 35, constrictor 304 is inserted in aorta 10 and can be used toremove thromboembolic material 72 from left common carotid artery 18,while augmenting and maintaining cerebral perfusion distal to theoccluding lesion. The occluder may be introduced through a guide sheathuntil it is positioned distal to left subclavian artery 20. In emergencysituations, the constrictor can be inserted through a femoral incisionin the emergency room, and atherectomy/suction catheter 402 can beinserted through the constrictor under angioscopic vision in theangiogram suite after the patient is stabilized hemodynamically. Theatherectomy/suction catheter, which includes expandable balloon 410,distal aspiration port 406, and atherectomy device 408, is introducedthrough opening 306 until its distal end is positioned in left commoncarotid artery 18 proximal to the thromboembolic occlusion.

Constrictor 304 is then expanded to partially occlude aortic blood flow,thereby increasing perfusion to the ischemic region distal to theoccluding lesion by enhancing ipsilateral collateral flow through leftexternal carotid artery 46 and left vertebral artery 34 andcontralateral collateral flow to right carotid artery 24 and rightvertebral artery 28. The variable flow mechanism of constrictor 304 canbe adjusted to control blood flow to the cerebral vasculature and theblood pressure. Balloon 410 of catheter 402 is expanded in the leftcommon carotid artery, thereby creating a closed chamber betweenconstrictor 410 and the thromboembolic occlusion. Suction can be appliedto aspiration port 406 to create a negative pressure in the closedchamber, thereby increasing the pressure differential across thethromboembolic occlusion, which may dislodge the occluding lesion ontothe aspiration port and remove the occluding lesion. Thromboembolicmaterial 72 may be further removed by atherectomy device 408. Themethods herein can also be used to remove thromboembolic occlusion inthe vertebral artery. The occlusion device 304, therefore, not onlyaugments cerebral perfusion in patients suffering from focal stroke orglobal ischemia, but also maintains cerebral perfusion while waiting forinvasive or noninvasive intervention. The devices and methods of usingatherectomy/suction catheter 102 are further described in U.S. Pat. No.6,165,199, incorporated herein by reference.

During abdominal aortic aneurysm (AAA) surgery, lumbar or spinalarteries, which provide blood supply to the spinal cord, are oftendissected away from the diseased abdominal aorta, resulting in reductionof blood flow to the spinal cord. The devices herein disclosed may beused to condition the spinal cord prior to AAA repair, thereby reducingthe damage resulting from spinal ischemia during surgery. In FIG. 36,constrictor 104 is inserted in aorta 10 and expanded preferably distalto left subclavian artery 20 and proximal to lumbar arteries 38. As aresult, blood flow to the lumbar or spinal arteries is reduced. Whenthis device is used in patients anticipating a major thoracoabdominalsurgery, such as AAA repair, approximately 24 hours prior to surgery,blood flow to the lumbar arteries can be intentionally reduced to inducemild spinal ischemia, thereby conditioning the spinal cord to produceneuroprotective agents which may protect the spinal cord from moresignificant ischemic insult during surgery.

In hypertension, end organ damage often results, e.g., cardiac, renal,and cerebral ischemia and infarction. The devices and methods herein maybe employed in hypertension to protect the kidneys from ischemic insult.In FIG. 37, constrictors 104, which can be introduced through a femoralartery, are inserted in right renal artery 80 and left renal artery 82.The constrictors are expanded to partially occlude blood flow fromdescending aorta 10 to the renal arteries, thereby reducing bloodpressure distal to the occlusion. The constrictors can be deployed forthe duration of any systemic hypertensive condition, thereby protectingthe kidneys from damage that might otherwise be caused by thehypertension.

In another embodiment, the constrictor will be provided withcapabilities for mounting on a standard catheter, e.g., a standardangioplasty balloon catheter, a stent deployment catheter, an ultrasoundcatheter, or an atherectomy catheter. Such a device having capabilitiesfor removable mounting on a standard catheter is depicted in FIGS.44A-44H. The constrictor shown in FIG. 44A includes elongate tubularmember 601 having lumen 605 for passage of blood extending from aproximal to a distal end of tubular member 601. The device includesconstrictor 602, here a balloon mounted on tubular member 601 andcommunicating with inflation lumen 603. Inflation lumen 603 extendsproximal, and extends through the incision in the patient so that itremains operable outside the patient's body. Tubular member 601 isconstructed of a flexible and deformable material so that inflation ofballoon 602 causes a reduction in the cross-sectional diameter of lumen605 as shown in FIG. 44B to reduce blood flow.

In use, tubular member 601 is positioned in the descending aorta andballoon 602 is inflated. The outer diameter of balloon 602 expands untilit engages the lumen of the descending aorta. Further inflation ofballoon 602 will cause deformation of tubular member 601 to therebyreduce lumenal diameter 605. In this manner, peripheral blood flow isreduced, resulting in an increase blood pressure upstream of the device.Because the device shown in FIGS. 44A and 44B is mounted on a standardcatheter (not shown), the standard catheter having diagnostic ortherapeutic capabilities extends beyond tubular member 601 and mayaccess any of the coronary arteries, carotid arteries, or any othervessels upstream of the descending aorta.

FIG. 44C depicts an alternative mountable constrictor having a shortenedtubular member 601, shortened by comparison with tubular member 601shown in FIG. 44A. FIG. 44D shows the constrictor of FIG. 44C withballoon 602 inflated. It should be noted that inflation of balloon 602proceeds until the outer diameter of balloon 602 engages the lumen ofthe aorta, whereupon further inflation causes deformation of tubularmember 601 inwardly to reduce the diameter of lumen 605, therebyconstricting blood flow.

In another embodiment, a removably mountable constrictor is provided asdepicted in FIGS. 44E and 44F. Referring to FIG. 44E, balloonconstrictor 602 communicates with a proximally extending inflation lumen(not shown), and balloon 602 includes first lumen 620 for passage ofblood, second lumen 615 for passage of a standard catheter, andmanometer 610. Blood flow lumen 620 is equipped with deformable walls621, shown in FIG. 44F at three different levels of deformation. Lumen615 is shaped to receive a standard catheter (angioplasty, stent,ultrasound, or atherectomy). Lumen 615 is also equipped with a lockingmechanism, shown here as first and second flexible clips 630 mounted ata position along lumen 615. In use, clips 630 are operated to clear apassage for advancement of a standard catheter through lumen 615. Theclips are then released to frictionally engage the catheter and therebyensure that the constrictor maintains a fixed position along thecatheter.

In another embodiment shown in FIGS. 44G and 44H, elongate tubularmember 601 having lumen 605 is constructed of a flexible deformablematerial. Spring 635 is disposed about an intermediate portion oftubular member 601. Spring 635 is operable between a relaxedconfiguration (FIG. 44H) and a constricted configuration (FIG. 44G). Thespring is operable by way of an actuating mechanism, such as a cinchstrap.

A stand alone coarctation device as depicted in any of FIGS. 44A-44H canbe mounted on a standard catheter as depicted in FIGS. 45A and 45B.Catheter 641 in FIGS. 45A and 45B carries stent 640 at a distal end ofcatheter 641. In other embodiments the catheter may carry an angioplastyballoon, an atherectomy device, and/or intravascular ultrasoundcapabilities. Catheter 641 passes through lumen 605 of elongate tubularmember 601. Catheter 641 is releasably engaged by tubular member 601 ina manner that allows open space for passage of aortic blood throughlumen 605. Balloon 602 is mounted circumferentially about tubular member601. In use, balloon 602 is inflated to engage the lumen of the aorta,and further inflation constricts the diameter of lumen 605, therebyreducing aortic blood flow. Tubular member 601 is constructed of adeformable material that allows inward flexing upon further inflation ofballoon 602.

A balloon having capabilities for purging gas is depicted in FIGS. 46Aand 46B. Introducer sheath 650 is disposed about balloon 602 tofacilitate entry into a major vessel, e.g., a femoral artery. Balloon602 communicates with first catheter 661 and second catheter 662, bothhaving a lumen extending to outside the patient's body. Saline isinjected through catheter 661 and fills balloon 662 through infusionport 663. Any gas within balloon 602 is purged through port 664 untilballoon 602 is entirely filled with saline. Air passes through catheter662 and exits the patient's body. Catheter 662 is then sealed, allowingballoon 602 to be inflated upon infusion of additional saline. Bloodflow lumen 605 is surrounded by a deformable wall. Balloon expansionengages the lumen of the aorta, and further expansion reduces thediameter of blood flow lumen 605, increasing blood pressure upstream ofthe coarctation device. FIG. 46B shows a cross-section of the cathetertaken through the balloon.

FIGS. 47A-47D depict alternative arrangements for partial aorticobstruction as contemplated herein. FIG. 47A shows a device that expandsradially outward, and where blood flows around the expandable member.FIG. 47B shows a device that expands inward, and where blood flowsthrough the expandable member. FIG. 47C shows a device that expandsoutward, and where blood flows through ports in the expandable member.FIG. 47D shows a device that expands outward, and where blood flows boththrough and around the expandable members.

FIG. 48 depicts a device that can be used as an adjunctive treatmentwhen combined with other technology to treat stroke. Catheter 102includes flexible distal region 172 adapted to access cranialvasculature. Catheter 102 includes a through lumen to passinterventional devices, e.g., micro-infusion catheters, pressure wires,stent catheters, angioplasty catheters, atherectomy devices,pharmaceuticals, cooling mechanisms, and alike. Distal end 172 issufficiently long to reach the vessels of the upper aortic arch. Theocclusion mechanism may comprise any of a variety of expandable membersas described in the various embodiments herein. Catheter 102 is shown incross-section in FIG. 48A. The catheter includes pressure lumen 161,proximal balloon inflation lumen 51, and distal balloon inflation lumen109. Main lumen 162 is, in certain cases, Teflon lined at surface 183,and 0.060 inches. Braid 182 reinforces catheter 102.

In use, as shown in FIG. 48, catheter 102 is positioned with balloon 104suprarenal, balloon 107 infrarenal, and pressure port 160 in between.The distal end 172 extends into the right brachiocephalic artery.Interventional instrument 175 passes through the lumen of catheter 102and is directed into right common carotid artery 174 for the purpose oftreating a lesion. Distal end 172 of catheter 102 may alternativelyaccess right subclavian artery 173, the right vertebral artery, theright internal carotid artery, the right external carotid artery, leftcommon carotid artery 176, the left internal carotid artery, the leftexternal carotid artery, left brachiocephalic artery 177, and/or theleft vertebral artery.

FIGS. 48B-48F depict a further alternative design. FIG. 48B showscatheter 102 having sufficient strength to resist the threes applied byblood flow during partial obstruction of the aorta, yet sufficientlyflexible to be easily inserted into the femoral artery and tracked intothe iliac and into the aorta. FIG. 48C is a cross-sectional view ofcatheter 102. FIG. 48D shows guiding catheter 178 with varying stiffnessalong its length. Distal most region 182 is soft, flexible andatraumatic. Intermediate region 183 is a transitionary stiffness zonefor introduction into the body. Proximal region 185 is very stiff andstabilizes the system. Bond 179 marks the insertion interface. Guidingcatheter 178 is slideably interfaced into lumen 162 of catheter 102depicted in FIG. 48B. The catheter 102 of FIG. 48B is, in certain cases,8 F compatible and approximately 70 cm in length. The guiding catheter178 shown in FIG. 48D is, in certain cases, a 5 F catheter andapproximately 100-120 cm in length to facilitate placement in thecerebral vasculature. The foregoing ranges are set forth solely for thepurpose of illustrating typical device dimensions. The actual dimensionsof a device constructed according to the principles of the presentinvention may obviously vary outside of the listed ranges withoutdeparting from those basic principles.

In use, guiding catheter 178 is inserted into lumen 162 of catheter 102until indicator band 179 is flushed with manifold 186 shown in FIG. 48E.A guidewire is placed within the aorta near the aortic arch. Theassembled device of FIG. 48E is then tracked over the guidewire.Contrast media can be injected through guiding catheter 178 to aidpositioning the device. Notably, the transitionary stiffness zone iswithin catheter 102 when assembled as shown in FIG. 48E. When catheter102 is properly positioned in the descending aorta, guiding catheter 178is further advanced up the descending aorta to engage a separatevasculature, e.g., coronary, carotid, or cerebral vasculature.Alternatively, at least partial obstruction of the aorta to increasecerebral blood flow may begin with the assembly as delivered, and at alater time guiding catheter 178 may be advanced.

EXAMPLE 1

In order to study the efficacy of the coarctation devices disclosedherein, an experiment was conducted using rats. The rat was placed underanesthesia, and an incision was made over one or more of the carotidarteries. The middle cerebral artery was ligated and the CCA was clampedusing a hemostat to abolish blood flow to the ipsilateral cerebralhemisphere, thereby inducing a stroke. The aorta was then ligated,thereby causing immediate and sustained elevation in the systolic bloodpressure (SBP), diastolic blood pressure (DBP), and mean arterialpressure (MAP) proximal to the constriction. It was found that theligation tended to produce doubling of MAP.

FIG. 38 shows a plot of cerebral blood flow (cc blood/100 grams braintissue/min) versus time (minutes) in a rate stroke model. Cerebral bloodflow (i) can be measured using Laser Doppler Flow (LDF) measurement. Asshown in FIG. 38, IPSI refers to the cerebral hemisphere where thestroke was induced, CONTRA refers to the cerebral hemisphere where thestroke was not induced (i.e., normal brain), and MBP refers to the meanblood pressure proximal to the aortic occlusion.

At “initiation,” the descending aorta was ligated. CBF is shown in FIG.38 to increase immediately following aortic ligation as indicated by therise in MBP. The rise in CBF can be seen at any level of placement ofthe ligation in the descending aorta, e.g., infrarenally orsuprarenally. Infrarenal placement of the coarctation devices may bepreferred since renal complications associated with occlusion of therenal blood supply are minimized, and prolonged use of the devices instroke patients is permitted. The increased CBF tended to fall over aforty-minute time period in some animals.

The CBF in the ipsilateral hemisphere is also shown in FIG. 38 toincrease immediately following ligation. Ipsilateral CBF on ligationincreased by approximately two times. The fact that any increase isobserved here is an unexpected result because this region of the brainrepresents the penumbra of the stroke. A five fold increase CBF in thecore of the stroke was also observed. This was highly unexpected. Theincreased ipsilateral CBF tends to fall in some animals over aforty-minute time period as well.

The CBF in the contralateral hemisphere is also shown to increaseimmediately following aortic ligation, as high as up to 500% of baselinevalue. The increased contralateral CBF also tends to fall over aforty-minute time period. The increase in perfusion was so marked thatthe devices described herein may only need to be inflated veryminimally, and the degree of inflation varied with time.

After “termination,” CBF is shown in FIG. 38 to fall immediately afterligation is released as indicated by the fail in MBP. The CBF in theipsilateral and contralateral hemispheres are also shown in FIG. 38 tofall immediately after ligation is released.

It was also noted that release followed by re-ligation of the aortareproduced the desired increase in CBF, even when the sequence wasrepeated several times. Thus, changes in MAP induce a hyperperfusionalstate best maintained by periodic re-inflation of the device (e.g.,twenty-minute periods of inflation with a few seconds of deflation inbetween as in the case for prolonged use of the coarctation device). Onehour of coarctation may be sufficient in treatment of stroke, and thusrepeated inflations would not be needed. Cerebral autoregulation duringaortic ligation was clearly overridden in this model. It is conceivablethat autoregulatory curves are quite different when blood pressure andCBF are increased using aortic constriction as compared to thoseobtained using injection of epinephrine, a cerebral vasoconstrictor.

This example further explains the important differences between aorticligation as described herein versus IABP. First, SBP increases when theaorta is ligated much more than SBP increases for IABP. Second, IABPincreases DBP but not SBP, and IABP pulls blood from the brain duringsystole. By contrast, ligation increases both DBP and SBP, and thereforeincreases cerebral blood flow at all times. Third, mean CBF is increasedfor ligation whereas mean CBF is unchanged for IABP. Ligationeffectively shifts the blood pressure curve upward at all points,systole and diastole. Fourth, ligation as described herein increasesblood flow in the brain during stroke by 100% or more, 200% or more,300% or more, 400% or more, and 500% or more. IABP by contrast, has beenshown to increase CBF by no more than 30-40% and in some studies hascaused a decrease in CBF by 10-12%. Fifth, the occlusion produced withIABP is inadequate for the purpose of treating stroke, since theincrease in cerebral perfusion is so marked during total occlusion that,the coarctation device will only need to constrict the aortic lumen,rather than occlude it.

Sixth, IABP provides sudden, jerky increases and decreases in bloodpressures, since inflation or deflation is an all or none process.Deflation of IABP is associated with sudden, severe drops in MAP tobelow baseline values and a corresponding dramatic fall in CBF, therebycausing dangerous hypoperfusion. Cyclical deflations and inflations ofIABP fail to provide a smooth and manipulable pressure proximally. Thecoarctation device disclosed herein incorporates a mechanism for a veryslow deflation to avoid the “rebound” hypoperfusion.

Seventh, EKG linkage and external pumping are essential for theoperation of IABP, but not required for the coarctation devices. Eighth,air embolization is a known complication of using IABP since air or gasis often used to inflate the balloon. The coarctation devices avoid airembolization by using liquid inflation or a spring mechanism. Tenth,spinal ischemia, aortic dissection, and renal ischemia are commoncomplications associated with high aortic positioning of IABP, e.g., atthe level of subclavian takeoff. Insertion and positioning of IABP oftenrequires fluoroscopy in an angiogram suite. The coarctation devices, onthe other hand, can be inserted either suprarenally or infrarenally. Theinfrarenal positioning avoids the complications associated with IABP andallows insertion of the coarctation devices in the ER without the use offluoroscopy. Eleventh, IABP is indicated in treatment of heart failureto boost coronary perfusion. By contrast, the coarctation devices can beused in treatment of stroke and non-cardiogenic shock to boost cerebralperfusion.

EXAMPLE 2

Sections of rat brain were taken before and after deployment of thedevices disclosed herein using fluorescent-labeled capillary perfusiontechniques. After induction of three-vessel stroke, the rat was injectedwith a red dye, followed by deployment of a coarctation device, followedby injection of a fluorescent green dye that has affinity for patentcapillary. The rat is then sacrificed and sections of the rat brain weretaken and exposed microscopically under fluorescent light. FIG. 39depicts a normal rat brain having numerous fluorescent stainingcapillaries.

In stroke induced rat model using the method described in Example 1, 10rats were used in a control group and 10 rats in a treatment group. Inthe control group (stroke but no coarctation) a fluorescent green dyewas injected prior to sacrificing the animal as described above. Adramatic reduction in the number of patent capillaries is evident in thestroke center as depicted in FIG. 40 and in the stroke penumbra of theipsilateral hemisphere as depicted in FIG. 41. In the rats treated withthe coarctation devices, the fluorescent dye is injected afterconstriction of the aorta. No cerebral hemorrhages were notedmicroscopically in the stroke center or the surrounding tissue. Thenumber of patent cerebral capillaries is clearly increased in thetreated rats using the coarctation devices, evident in the stroke centeras depicted in FIG. 42 and in the stroke penumbra as depicted in FIG.43. A comparison of the stroke control using green dye, for which therewere eight open blood vessels, to the group treated with coarctation,for which there were 20 open vessels, shows that coarctation opened morethan 100% more capillaries. This example further demonstrates theefficacy of using the coarctation devices in improving cerebral bloodflow for treatment of stroke.

EXAMPLE 3 Infarct Volume Reduction Using Coarctation Device

Using the TTC technique (technetium stain) to determine infarct (stroke)volume, one hour of treatment with a coarctation device inflated at thelevel of the kidneys, and started 90 minutes after the onset of stroke(induced by CCA and MCA occlusion plus occlusion of contralateralcarotid artery plus occlude CCA on good side for one hour), reducedstroke volume at 24 hours from 1100 to 400. Thus, one hour of treatmentachieved a 66% reduction in stroke volume. In certain animals, up to 80%reduction in stroke volume was achieved, and the stroke was not visibleat low magnification. Thus, the devices and methods disclosed hereinprovide for a reduction in stroke volume of at least 60%, morepreferably at least 70%, more preferably at least 80%, and mostpreferably greater than 80%.

EXAMPLE 4 Use of Coarctation Device in Dryden Dogs

A coarctation device as depicted in FIG. 2B, consisting of a balloonwith a central passage allowing blood flow through it, was introducedtransfemorally into the aorta. Correct placement was confirmed byfluoroscopy by injecting dye into balloon 104. An inflation of 1-3 ccprovides incomplete occlusion, allowing blood passage through the centerand around the edges of the device. At 4-5 cc inflation, blood onlyflows through the center of the device. Blood pressure above and belowthe device was recorded. The effect of the device in different positions(infrarenal, suprarenal, supracoeliac, and thoracic) on blood pressurewas noted. The effect of changes in blood volume on pressure atdifferent levels of constriction was examined (shock induced byhemorrhage). Infrarenally, 17-25% increased pressure was noted startingat 3 cc of inflation, which correlates with incomplete occlusion. Thisincrease in pressure is sustainable. Suprarenally, 50-60% increasedpressure was noted starting at 3 cc of inflation, which correlates withincomplete occlusion. This increase in pressure is sustainable. Furtherinflations either suprarenally or infrarenally will not increase bloodpressure and cause bulging of the aorta outward.

Although the foregoing invention has, for the purposes of clarity andunderstanding, been described in some detail by way of illustration andexample, it will be obvious that certain changes and modifications maybe practiced which will still fall within the scope of the appendedclaims.

What is claimed is:
 1. A method for increasing cerebral blood flow,comprising the steps of: inserting a catheter into a descending aorta,the catheter having a proximal end, a distal end, a first inflatableballoon mounted on the distal end, and a second inflatable balloonmounted on the distal end proximal the first inflatable balloon;locating the first inflatable balloon upstream from a takeoff of renalarteries; locating the second inflatable balloon downstream from thetakeoff of the renal arteries; and inflating and maintaining an inflatedstate of the second inflatable balloon to partially occlude blood flowin the descending aorta during systole and diastole, wherein cerebralblood flow is increased.
 2. The method of claim 1, wherein the secondinflatable balloon is adjusted in volume to achieve a desired bloodpressure gradient from one side to the other of the second inflatableballoon, while maintaining partial occlusion of the aorta.
 3. The methodof claim 2, further comprising the step of inflating and maintaining aninflated state of the first inflatable balloon to partially occludeblood flow in the aorta during systole and diastole.
 4. The method ofclaim 3, wherein the first balloon is adjusted in volume to achieve adesired blood pressure gradient from one side to the other of saidballoon, while maintaining partial occlusion of the aorta.
 5. The methodof claim 4, further comprising the step of inflating and maintaining thefirst and second balloons for at least 30 minutes.
 6. The method ofclaim 5, further comprising the step of inflating and maintaining thefirst and second balloons for at least one hour.
 7. The method of claim1, wherein the second inflatable balloon is inflated to provide 50% orgreater occlusion of the cross-sectional area of the descending aorta.8. The method of claim 7, wherein the second inflatable balloon isinflated to provide 56% or greater occlusion of the cross-sectional areaof the descending aorta.
 9. The method of claim 8, wherein the secondinflatable balloon is inflated to provide 64% or greater occlusion ofthe cross-sectional area of the descending aorta.
 10. The method ofclaim 9, wherein the second inflatable balloon is inflated to provide71% or greater occlusion of the cross-sectional area of the descendingaorta.
 11. The method of claim 10, wherein the second inflatable balloonis inflated to provide 76% or greater occlusion of the cross-sectionalarea of the descending aorta.
 12. The method of claim 11, wherein thesecond inflatable balloon is inflated to provide 83% or greaterocclusion of the cross-sectional area of the descending aorta.
 13. Themethod of claim 12, wherein the second inflatable balloon is inflated toprovide 91% or greater occlusion of the cross-sectional area of thedescending aorta.
 14. The method of claim 1, further comprising the stepof inflating and maintaining an inflated state of the first inflatableballoon to partially occlude blood flow in the aorta during systole anddiastole.
 15. The method of claim 14, wherein the first balloon isadjusted in volume to achieve a desired blood pressure gradient from oneside to the other of said balloon, while maintaining partial occlusionof the aorta.
 16. The method of claim 14, further comprising the step ofinflating and maintaining the first and second balloons for at least 30minutes.
 17. The method of claim 16, further comprising the step ofinflating and maintaining the first and second balloons for at least 1hour.
 18. The method of claim 14, wherein the first inflatable balloonis inflated to provide 50% or greater occlusion of the cross-sectionalarea of the descending aorta.
 19. The method of claim 18, wherein thefirst inflatable balloon is inflated to provide 56% or greater occlusionof the cross-sectional area of the descending aorta.
 20. The method ofclaim 19, wherein the first inflatable balloon is inflated to provide64% or greater occlusion of the cross-sectional area of the descendingaorta.
 21. The method of claim 20, wherein the first inflatable balloonis inflated to provide 71% or greater occlusion of the cross-sectionalarea of the descending aorta.
 22. The method of claim 21, wherein thefirst inflatable balloon is inflated to provide 76% or greater occlusionof the cross-sectional area of the descending aorta.
 23. The method ofclaim 22, wherein the first inflatable balloon is inflated to provide83% or greater occlusion of the cross-sectional area of the descendingaorta.
 24. The method of claim 23, wherein the first inflatable balloonis inflated to provide 91% or greater occlusion of the cross-sectionalarea of the descending aorta.